A group of investigators of the Wistar Institute and of the University of Pennsylvania proposes to install a workstation for peptide synthesis and analysis. Initially the equipment should include an automated peptide synthesizer, reversed-phase gradient high performance liquid chromatography (HPLC) system and an amino acid analyzer. The investigators follow a probe-driven approach in addressing such biological problems as chemical and conformational requirements for T-cell epitopic regions of proteins, development of synthetic vaccines and identification of abnormally processed protein structures that are involved in the formation of senile plaques and neurofibrillary tangles, hallmark lesions of Alzheimer's disease. The proposed workstation will be used to synthesize peptides to be used as tools for these projects, and at the same time the investigators understand the importance of new methodology in the development of novel peptide synthetic and analytic strategies. The Wistar Institute has successfully developed solid-phase methods for unmodified peptides, N-glycopeptide and O-phosphopeptide synthesis, a unique achievement, and is in the process of improving these techniques. To obtain pure peptides and develop new methodologies the purification of both modified and unmodified peptides is accomplished by reversed-phase HPLC. HPLC also provides structural information about the synthesized peptides. Amino acid analysis is needed not only for structure verification but as a continuous control of the synthetic processes. The proposed workstation will serve as a basis of an interactive relationship between peptide synthesis, analysis and application. Prompt, onsite modifications in peptide structure can be made to meet the challenges of the sequential steps of the interactive approach. The workstation will also ease the increasing demands made by the investigators for custom-made synthetic peptides that are not accessible through the Institute's core facilities. The proposed workstation will further guarantee attainment of the goals proposed by the investigators in their current PHS supported projects.